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Pharmacogenetics of anticoagulants.

Rane A, Lindh JD - Hum Genomics Proteomics (2010)

Bottom Line: Here, we describe particulars of the relative pharmacogenetic influence on the kinetics of these agents, the population distribution of genetics risk groups, and novel data on clinical features with influence on dose requirement and ADR risk.The usefulness of genetic information prior to and soon after start of therapy is also discussed.The current renewed focus on these issues is caused not only because of new genetic knowledge and genotyping facilities but also because of the high rate of serious ADRs.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden.

ABSTRACT
Warfarin, acenocoumarol, and phenprocoumon are among the major anticoagulant drugs worldwide. Because of their low therapeutic index and serious adverse reactions (ADRs), their wide use, and their varying kinetics and pharmacogenetic dependence, it is of great importance to explore further possibilities to forecast the dose beyond conventional INR measurements. Here, we describe particulars of the relative pharmacogenetic influence on the kinetics of these agents, the population distribution of genetics risk groups, and novel data on clinical features with influence on dose requirement and ADR risk. The usefulness of genetic information prior to and soon after start of therapy is also discussed. The current renewed focus on these issues is caused not only because of new genetic knowledge and genotyping facilities but also because of the high rate of serious ADRs. Application of these measures in the care of patients with anticoagulant therapy is important awaiting new therapeutic principles to be introduced, which may take long time still.

No MeSH data available.


Related in: MedlinePlus

Cumulative incidence of severe bleeding and the composite of severe bleeding and all-cause mortality in the warfarin-treated WARG cohort [5].
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2958670&req=5

fig1: Cumulative incidence of severe bleeding and the composite of severe bleeding and all-cause mortality in the warfarin-treated WARG cohort [5].

Mentions: We embarked upon a prospective study of patients in need of anticoagulation because of atrial fibrillation, deep venous thrombosis, pulmonary emboli, and so forth [5]. In our prospective study, warfarin naïve patients consented to donate a blood sample for genotyping at the start of warfarin treatment. The study included 1523 patients. All of them were monitored according to local clinical routines at 40 different study sites in Sweden. Warfarin bleedings defined according to WHO definition of severe adverse drug reaction [6] as well as other adverse reactions were reported to the study centre where the blood samples were stored in a biobank sample collection. In this cohort of patients starting treatment with warfarin, the incidence of first-time severe haemorrhage was 2.3 per 100 patient years (95% confidence interval 1.4–3.1). During a mean followup time of 10 months, 1.8% of the included patients died and the overall incidence of severe bleeding or death (all-cause) was 4.3 per 100 patient years (95% c.i. 3.2–5.5) (Figure 1). Our assessment of the incidence was lower than has been reported earlier [7–9], probably because of the more strict criteria stipulated by WHO and applied by us.


Pharmacogenetics of anticoagulants.

Rane A, Lindh JD - Hum Genomics Proteomics (2010)

Cumulative incidence of severe bleeding and the composite of severe bleeding and all-cause mortality in the warfarin-treated WARG cohort [5].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2958670&req=5

fig1: Cumulative incidence of severe bleeding and the composite of severe bleeding and all-cause mortality in the warfarin-treated WARG cohort [5].
Mentions: We embarked upon a prospective study of patients in need of anticoagulation because of atrial fibrillation, deep venous thrombosis, pulmonary emboli, and so forth [5]. In our prospective study, warfarin naïve patients consented to donate a blood sample for genotyping at the start of warfarin treatment. The study included 1523 patients. All of them were monitored according to local clinical routines at 40 different study sites in Sweden. Warfarin bleedings defined according to WHO definition of severe adverse drug reaction [6] as well as other adverse reactions were reported to the study centre where the blood samples were stored in a biobank sample collection. In this cohort of patients starting treatment with warfarin, the incidence of first-time severe haemorrhage was 2.3 per 100 patient years (95% confidence interval 1.4–3.1). During a mean followup time of 10 months, 1.8% of the included patients died and the overall incidence of severe bleeding or death (all-cause) was 4.3 per 100 patient years (95% c.i. 3.2–5.5) (Figure 1). Our assessment of the incidence was lower than has been reported earlier [7–9], probably because of the more strict criteria stipulated by WHO and applied by us.

Bottom Line: Here, we describe particulars of the relative pharmacogenetic influence on the kinetics of these agents, the population distribution of genetics risk groups, and novel data on clinical features with influence on dose requirement and ADR risk.The usefulness of genetic information prior to and soon after start of therapy is also discussed.The current renewed focus on these issues is caused not only because of new genetic knowledge and genotyping facilities but also because of the high rate of serious ADRs.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden.

ABSTRACT
Warfarin, acenocoumarol, and phenprocoumon are among the major anticoagulant drugs worldwide. Because of their low therapeutic index and serious adverse reactions (ADRs), their wide use, and their varying kinetics and pharmacogenetic dependence, it is of great importance to explore further possibilities to forecast the dose beyond conventional INR measurements. Here, we describe particulars of the relative pharmacogenetic influence on the kinetics of these agents, the population distribution of genetics risk groups, and novel data on clinical features with influence on dose requirement and ADR risk. The usefulness of genetic information prior to and soon after start of therapy is also discussed. The current renewed focus on these issues is caused not only because of new genetic knowledge and genotyping facilities but also because of the high rate of serious ADRs. Application of these measures in the care of patients with anticoagulant therapy is important awaiting new therapeutic principles to be introduced, which may take long time still.

No MeSH data available.


Related in: MedlinePlus